When you think about it after the twins were born, something must have happened to their mother after they were born. And we have Sesshomaru, who went to pick his own daughters up. We only have Kaede's word on his actions, but the fact that he picked them up right after their birth has tragic implications.
And then we find Rin inside the Tree of Ages. Something must have happened to her that made Sesshomaru desperate enough to revive her again, after his mother went to great pains to tell him he can't always save her life.
The fact that something has happened to Inuyasha and Kagome that caused them to not be around their daughter growing up is heartbreaking. Likewise for Moroha having to have grown up without her parents, and apparently doesn't even know who they are or have any memories of them.
Adding in, is that so far all 3 of the girls not only aren't aware of who their parents are but honestly don't seem to care about it or interested in learning about them.
Episode 2
Towa and Setsuna being separated during a forest fire that separated them. Towa unintentionally had let go of Setsuna's hand, and then she was sent into Reiwa Japan by herself. The only consolation she's gotten is being adopted by Sota and Moe Higurashi and has an adopted little sister.
Episode 3
Towa finally reunites with Setsuna, she is unapproachable and hostile, but also she doesn't remember her older twin sister.
What's even more of a punch in the gut is when Moroha reveals that Setsuna literally cannot sleep due to the Dream Butterfly that has eaten her dreams, as well as her memories. Towa's reaction when she hears about it is very understandable.
Towa gets in between Setsuna, trying to gouge Mei's possessed eye, and a possessed Mei, saying she can't trouble the Higurashis any more than she already has. She later says that Mei getting possessed is all her fault.
Episode 7
Towa has joined the Demon Hunter clan and is working with Setsuna, Hisui, and the others. When she goes to sleep, she wakes up to find that they left without her to go on a mission. She is very hurt by this and decides to go off looking for the Dream Butterfly by herself.
Episode 8
Takechiyo's dream showing Kagome saying goodbye to baby Moroha before sending her away to save her from a battle with Kirinmaru and Sesshomaru.
Kagome's wording implies that she didn't expect to survive the fight which considering that she and Inuyasha never came to retrieve her, suggests that that may be the case.
Kagome gives Moroha the rouge that belonged to Inuyasha's mother and mentions how "We decided that if we had a girl, we would give this to her." Just the fact that Inuyasha and Kagome must have been so excited about expecting and talking about what gender their baby would make it all the more heartbreaking. They didn't even get a few years with Moroha which many fans had hoped for, she was taken from them as an infant.
Episode 9
Despite her Genki Girl attitude, Moroha is revealed to actually be quite lonely having grown up by herself and is rather heartbroken when her cousins and newfound friends Towa and Setsuna initially don't want to tag along with her on a bounty hunting job, clearly thinking that they don't actually care about her.
Meioju's son was only able to run when Konton killed his father for his armor, and has spent the last ten years following the Peril around, trying to find a way to avenge him.
Episode 10
Kinka and Ginka belong to a demonic tribe of Conjoined Twins, where each demon is supposed to duel their twin until one wins, then absorb their flesh and take their entire body for themselves, but the two of them are too evenly matched. They steal Setsuna and Towa's Rainbow Pearls in an attempt to break the tie, but their clan leader Joka betrays them and attempts to consume them in an attempt to gain enough power for Revenge on Sesshōmaru. Kinka is torn from his brother as Joka decides to absorb him first, and though Ginka tries to rescue him with the help of the twins, he ends up dying, with Ginka following soon after, admitting that deep down, he knew that they'd end up dying together.
Episode 11
When Towa berates an older brother for trying to challenge the demon in a pond that ate the parents of him and his sister, she makes a comment about not letting go of a sister's hand no matter what, clearly channeling her regret at Setsuna's hand slipping from her own grasp all those years ago.
Episode 12
Towa is rendered helpless by the new moon, forcing her sister and cousin to protect her.
Episode 13
Hisui has come to view his father Miroku as a coward due to him choosing to go into the mountains for a 1000-day training regiment to increase his power. Thankfully, they repair their relationship by the end of the episode.
Episode 15
The Black Pearl to the Great Dog Demon's grave was completed so fast partially because the grief of Inuyasha's mother, still lingering strong centuries after her death, was used as a catalyst.
Sesshomaru taking away his newborn daughters from their mother, Rin, as Zero has threatened him moments ago that Kirinmaru is sure to kill them SHOULD he find out about them. Rin can only look on and trust in him as he flies away with their twins. Doesn’t stop her from shedding some Tender Tears.
Episode 16
The fate of Yawaragi, Moroha's mentor. Konton creates a situation where the teacher and her former student are forced to fight to the death. When Moroha uses her powerful Crimson Backlash Wave, Yawaragi tries a Taking You with Me gambit with Konton, but he escapes. As Yawaragi dies, she tells Moroha how proud she is of her.
Episode 20
When in her berserk state for the first time, Setsuna nearly attacked Shiori and the other children defending the village. Luckily Miroku was there to stop her.
When Miroku asks about Shiori's mother, Shizu, we learn that she passed away from an illness some time ago. Particularly wrenching since she and her daughter were finally able to live together in the original series.
Episode 23
When Zero is murdered by Setsuna, we see Rin wake up, but look as if she is about to drown. Sesshomaru is visibly shocked at this runs to immediately revive Zero, so as to prevent Rin's potential death. One can only imagine how devastated Sesshomaru would be knowing that Rin, more so than their children, can't be revived again.
Episode 24
When fighting Kirinmaru, Setsuna manages to get a blow on him. However, he retaliates and slashes Setsuna, killing her on the spot. Towa spends the rest of the fight in a sorrowful rage.
When Towa is holding the dying Setsuna, her limp hand slips through Towa's as she expires, devastating Towa because she let her hand go again.
Moroha also flies into a rage when Kirinmaru kills Setsuna as her cousins are the first friends she has had in her life and she loses one of them.
Kirinmaru himself actually laments the incident as well, even wishing the Tenseiga wasn't broken so that she could be revived. The entire incident was reflex, one he regretted acting upon, and given his reverence for their grandfather, it's not a surprise.
Heck, the end of the episode is as bleak as hell, as Kirinmaru not only wins, he has no lasting damage done to him, leaving him to live to fight another day, and with the Tenseiga destroyed, Setsuna stays dead with no hope for revival, leaving Moroha to grieve the fact that they she and Towa were not able to avenge her, while Towa breaks down and starts sobbing over her dead sister in the rain. Even the "Ray of Hope" Ending of Sesshomaru giving Towa the broken Tenseiga doesn't alleviate it, since the following episode in Season 2 wouldn't air for another 7 months until October.
Episode 39
Moroha's reunion with her parents ends with her unable to process the feelings she's having, especially from her father, Inuyasha, she breaks down in tears. They're partly Tears of Joy, but mostly they're tears of sheer anguish from being denied this love for all her life. Her cousins and mother start crying at it, even Inuyasha is Trying Not to Cry, but its clear Moroha's Cry into Chest is her just trying to come to terms with what she's lost and now regained.
Inuyasha trying to not to cry doubles down when you remember that his father died on the day of his birth and he significantly outlived his mother to the point of being on his own when he was still a child. He knows what it's like to be an orphan. He didn't want that for Moroha and yet here she is, a teenager, who never knew him or Kagome. From the moment he picks her up until the "how do we escape" plot kicks in, he doesn't let her go, even carrying her. Its pretty clear what's going through his mind through it all.
Kagome gets her own. While it is a heartwarming moment for her to get caught up on what's happening in Reiwa-era Japan, her reactions to things may seem a bit odd with odd segues into things like how youthful she's been kept by staying in her Father-in-Law's tomb (aka freezing her aging). Thing is, this was her reaction to bad news in the old series, but we heard her thoughts then too as she processed them. We're not hearing them this time. So why would she react that way? Well the one she reacts that way the hardest to is Sota, her little brother... except he was only a few years younger than her and her age froze in her mid-twenties. He's in his thirties. She's the little sibling now. Never mind that nearly 20 years in present day has passed (which would be alot to take in), now even if she returned to it, she could never have the same dynamic with her family ever again. Yet another thing Sesshomaru and Kirinmaru have stolen from her.
While the twins are both shedding Tears of Joy at Moroha's reunion with her family, Setsuna (who was revived in the beginning of Season 2) is crying considerably more than Towa as she grabs her sister's hand. You can tell that she's clearly thinking of her own reunion with Towa, and how she spent a decade away from her beloved sister after the fire and then had her childhood memories taken away.
Episode 45
Towa saying goodbye to her family in the modern era, especially with Mei trying not to cry. Though, not without its heartwarming moments:
Sota: Towa... I think of you... as my actual daughter. I always have, and I always will. Towa, you will always be my daughter.
Manga
A small bouquet of flowers is shown lying on the Bone Eater's Well. It really drives home the fact that, baring some magic or other, Kagome's family would never see her again and that she would die centuries in the past.
